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BackgroundMalignant pleural mesothelioma (MPM) is an aggressive malignancy without curative treatment. Standard of care (SOC) include pemetrexed/cisplatin and nivolumab/ipilimumab with median overall survival in unresectable disease of 12.1 months and 18.1 months respectively.1 2 ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic adenovirus (Ad5/3-D24-GMCSF) with a unique ability to both prime and boost immune responses. The aim of the study was to assess efficacy and safety of ONCOS-102 in combination with SOC chemotherapy in 1st and 2nd line unresectable MPM.MethodsTwenty patients (experimental arm) were allocated to receive ONCOS-102 given intratumorally under CT or US guidance at a dose of 3 x 1011 VP on Day 1, 4, 8, 36, 78 and 120 plus six cycles of SOC starting on Day 22. Eleven patients (control group) received SOC. Imaging was done at baseline, Day 43–64 and 127–148 with regular monitoring of blood and biopsy based immune markers. Primary objective was safety and tolerability. Secondary objectives were ORR, PFS and OS as well as immunological activation. An analysis of 24 month survival data compared randomised only patients excluding six patients in the single-arm safety lead-in.Results24-month survival rate for 1st line pts was 50% in the experimental group and 0% in the control group with mOS of 25.0 months and 13.5 months respectively (N.S). Based on censoring, mOS in the experimental group will be within 21.9 – 25.0 months range. mOS across both 1st and 2nd line was 19.3 and 18.3 months for experimental and control patients (N.S). mPFS was 9.8 months in the experimental group and 7.6 in the control group (N.S.).ConclusionsThe survival rate of patients receiving ONCOS-102 in combination with SOC was seen to be numerically higher than previously reported for SOC or nivolumab/ipilimumab. Improved survival was associated with ONCOS-102 induced immune activation with a favourable TME modulation providing scientific rationale for combination with check point inhibition.Trial RegistrationClinicalTrials.gov NCT02879669ReferencesVogelzang, et al, Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21: 2636–44.Baas P, et al, First-line nivolumab plus ipilimumab in unresectable pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. The Lancet 2021; 397: 375–386.Ethics ApprovalThis study was approved by the IRBs of all the participating sites in Madrid, Barcelona, Rennes and Poitiers.

Cancer therapy; Mesothelioma Terapia del cáncer; Mesotelioma Teràpia del càncer; Mesotelioma CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. Clinical records of all MPM patients diagnosed at Vall d’Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan–Meier method. 189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95% CI 17.2–24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in non-epithelioid patients (HR 2.25 CI 95% 1.4–3.4; p

Background Tumour heterogeneity impacts the efficacy of metastatic cancer treatment even if actionable mutations are identified. Clinicians need to understand if assessing one lesion provides reliable information to drive a therapeutic decision in non-small-cell lung cancer (NSCLC) patients. Methods We analysed inter-tumour heterogeneity from five autopsied individuals with NSCLC-harbouring mutations in the epidermal growth factor receptor (EGFR), treated with EGFR tyrosine kinase inhibitors (TKIs). Through a comprehensive next-generation sequencing (NGS) oncopanel, and an EGFR panel for digital droplet PCR (ddPCR), we compared metastases within individuals, longitudinal biopsies from the same lesions and, whenever possible, the primary naive tumour. Results Analysis of 22 necropsies from five patients revealed homogeneity in pathogenic mutations and TKI-resistance mechanisms within each patient in four of them. In-depth analysis by whole-exome sequencing from patient 1 confirmed homogeneity in clonal mutations, but heterogeneity in passenger subclonal alterations. Different resistance mechanisms were detected depending on the patient and line of treatment. Three patients treated with a c-MET inhibitor in combination with TKI lost MET amplification upon progression. Conclusion At a given point and under selective TKI pressure, a single metastasis biopsy in disseminated tumours from EGFR-mutated NSCLC patients could provide a reasonable assessment of actionable alterations useful for therapeutic decisions.

Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response. We assembled a retrospective cohort of 262 NSCLC patients treated with ICIs, compiled relevant clinicopathological characteristics, and studied their associations with treatment outcome using Cox proportional-hazards survival models. Additionally, we investigated the interrelations between clinicopathological features and devised a method to create a compendium associated with ICIs response by selecting those that provide non-redundant information. In multivariate analyses, ECOG performance status (hazard ratio (HR) 1.37 (95% CI 1.11 to 1.68), p &lt, 0.005), LDH (HR 1.24 (95% CI 1.03 to 1.48), p = 0.02)) and PD-L1 negativity were associated with decreased PFS (HR 1.92 (95% CI 1.03 to 3.58), p &lt, 0.04), whereas presentation of immune-related adverse events (irAEs) (HR 0.35 (95% CI 0.22 to 0.55, p &lt, 0.005) or females (HR 0.52 (95% CI 0.33 to 0.80, p &lt, 0.005) had longer progression-free survival. Additionally, numerous clinicopathological indicators were found to be interrelated. Thus, we searched for features that provide non-redundant information, and found the combination of LDH levels, irAEs, and gender to have a better association with ICIs treatment response (cross-validated c-index = 0.66). We concluded that several clinicopathological features showed prognostic value in our real-world cohort. However, some are interrelated, and compendiums of features should therefore consider these interactions. Joint assessment of LDH, irAEs, and gender may be a good prognostic compendium.

Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future., E. Nadal thanks the support of Health Institute Carlos III-FEDER (ISCIII) [PI14/01109 and PI18/00920].

Background Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients. Methods NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n = 118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy. Discussion Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy. Trial registration: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&draw=2&rank=1.

Background Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy without curative treatment. Majority of patients receive pemetrexed/cisplatin as standard of care (SoC). Median overall survival in unresectable disease is 12 months. ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic adenovirus (Ad5/3-D24-GMCSF) with a unique ability to both prime and boost immune responses. The aim of the study was to assess immune and clinical responses as well as safety in patients with 1st and 2nd line unresectable MPM. Methods Eligible patients (experimental arm, n=20) received ONCOS-102 given intratumorally under CT or US guidance at a dose of 3 × 10 × 11 on Day 1, 4, 8, 36, 78 and 120 plus six cycles of SoC starting on Day 22. The control group (n=11) received only SoC. Imaging was done at baseline, Day 43–64 and 127–148. Patients were monitored regularly for immunological assessment including lesional biopsies (baseline and Day 36). Primary objective was safety and tolerability. Secondary objectives were immunological activation, ORR, PFS and OS as well as correlation between immunological activation and clinical outcome. Results There were no safety concerns nor DLTs. In 1st line patients ORR/DCR was 30%/90% in the experimental group and 33%/83% in the control group. 2nd line patients had ORR/DCR of 11%/67% in the experimental group and 60%/80% in the control group. 12-month survival rate for the 1st line pts was 64% in the experimental group and 50% in the control group. PFS and OS are still to be reported. The treatment with ONCOS-102 induced strong upregulation of multiple genes associated with immune activation in tumor lesions. Profound innate and adaptive immune activation was observed in the experimental vs control group that was associated with better clinical outcome. In addition to an increase in intra-tumoral cytotoxic T-cells (10/15 pts), the treatment with ONCOS-102 resulted in polarization from M2 to M1 macrophages. An upregulation of PD-L1 was reported in 9/15 pts in the experimental group vs 2/5 pts in the control arm, highlighting the potential of ONCOS-102 as an immunosensitizing agent for combinatory therapies with checkpoint inhibitors. Conclusions ONCOS-102 treated patients benefited from superior immune activation compared to patients receiving SoC with preliminary signals of clinical efficacy. Upregulation of adaptive immunity and cytotoxicity related gene expression, PD-L1 level and M2 to M1 macrophage polarization indicate that ONCOS-102 can induce a favourable TME modulation thus providing a scientific rationale for combination with check point inhibition. Trial Registration ClinicalTrials. gov NCT02879669 Ethics Approval This study was approved by the IRBs of all the sites in Madrid, Barcelona, Rennes and Poitiers.

Introduction Uncommon epidermal growth factor receptor (EGFR) mutations (u-EGFRm) are a heterogeneous group of molecular alterations and have also been reported as comutations with other EGFR mutations (complex mutations) in non–small-cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, and we examined its efficacy in Spanish clinical practice. Patients and Methods Data of 67 patients with advanced NSCLC with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. u-EGFRm were analyzed as complex mutations (group A), EGFR exon 20 insertions (ins20; group B), or single mutations (group C). Efficacy was evaluated in terms of overall survival (OS) and tumor response. Results Group A complex u-EGFRm consisted of double mutations of G719X+E709F, G719X+S768I, G719X+L861Q, L858R+T790M, L858R+S768I, L858R+S765I, del19+S768I, del19+L747S, or R776C+L861Q. No differences in clinical characteristics were found between groups A (n = 20), B (n = 23), and C (n = 24). Afatinib was administered as first-line therapy in 80% of patients. Median time of receipt of therapy was 4.2 months (range, 2.0–12.9 months). Median OS for the entire cohort was 19.9 months (95% confidence interval, 9.7, 30.1). Hazard ratios for OS were 0.26 (95% confidence interval, 0.10, 0.71; P = .008) and 0.40 (95% confidence interval, 0.17, 0.95; P = .037) for groups A and C compared to B, respectively. Response was significantly higher in groups A (70%) and C (54%) compared to B (13%; pairwise comparison P Conclusion In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.

Immune checkpoint inhibitors are considered standard second-line treatment in advanced non-small cell lung cancer patients. This strategy has also become standard in first-line setting for a subgroup of patients with strongly positive PD-L1 tumors; therefore, PD-L1 status might be considered a new biomarker that deserves upfront testing. New combinations of immune checkpoint inhibitors and with chemotherapy have been tested in first-line treatment. However, some questions remain unanswered such as the best treatment strategy or the real upfront efficacy of these therapeutic strategies in the whole lung cancer population. In this review we summarize the main results in the first-line setting of recent phase III trials with immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

New therapeutic strategies for malignant mesothelioma are urgently needed. In the DETERMINE study, we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma.DETERMINE was a double-blind, placebo-controlled, phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease. Eligible patients were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and measurable disease as defined in the modified Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma. Patients were randomly assigned (2:1) in blocks of three, stratified by European Organisation for Research and Treatment of Cancer status (low risk vs high risk), line of therapy (second line vs third line), and anatomic site (pleural vs peritoneal), by use of an interactive voice or web system, to receive intravenous tremelimumab (10 mg/kg) or placebo every 4 weeks for 7 doses and every 12 weeks thereafter until a treatment discontinuation criterion was met. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is ongoing but no longer recruiting participants, and is registered with ClinicalTrials.gov, number NCT01843374.Between May 17, 2013, and Dec 4, 2014, 571 patients were randomly assigned to receive tremelimumab (n=382) or placebo (n=189), of whom 569 patients received treatment (two patients in the tremelimumab group were excluded from the safety population because they did not receive treatment). At the data cutoff date (Jan 24, 2016), 307 (80%) of 382 patients had died in the tremelimumab group and 154 (81%) of 189 patients had died in the placebo group. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7·7 months (95% CI 6·8-8·9) in the tremelimumab group and 7·3 months (5·9-8·7) in the placebo group (hazard ratio 0·92 [95% CI 0·76-1·12], p=0·41). Treatment-emergent adverse events of grade 3 or worse occurred in 246 (65%) of 380 patients in the tremelimumab group and 91 (48%) of 189 patients in the placebo group; the most common were dyspnoea (34 [9%] patients in the tremelimumab group vs 27 [14%] patients in the placebo group), diarrhoea (58 [15%] vs one [1%]), and colitis (26 [7%] vs none). The most common serious adverse events were diarrhoea (69 [18%] patients in the tremelimumab group vs one [1%] patient in the placebo group), dyspnoea (29 [8%] vs 24 [13%]), and colitis (24 [6%] vs none). Treatment-emergent events leading to death occurred in 36 (9%) of 380 patients in the tremelimumab group and 12 (6%) of 189 in the placebo group; those leading to the death of more than one patient were mesothelioma (three [1%] patients in the tremelimumab group vs two [1%] in the placebo group), dyspnoea (three [1%] vs two [1%]); respiratory failure (one [1%] vs three [2%]), myocardial infarction (three [1%] vs none), lung infection (three [1%] patients vs none), cardiac failure (one [1%] vs one [1%]), and colitis (two [1%] vs none). Treatment-related adverse events leading to death occurred in five (1%) patients in the tremelimumab group and none in the placebo group. The causes of death were lung infection in one patient, intestinal perforation and small intestinal obstruction in one patient; colitis in two patients, and neuritis and skin ulcer in one patient.Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors. Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing.AstraZeneca.

Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1–26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5–18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil–lymphocyte ratio (NLR)

Background Nintedanib targets VEGF receptors 1-3, PDGF receptors alpha and beta, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma. Methods This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged >= 18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100. Findings Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5.3 months (IQR 2.8-7.3) in the nintedanib group and 5.1 months (2.7-7.8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6.8 months [95% CI 6.1-7.0]) and the placebo group (7.0 months [6.7-7.2]; HR 1.01 [95% CI 0.79-1.30], p=0.91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]). Interpretation The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

e20563 Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. Histology is a prognostic factor and recently CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line with some differences in the efficacy of chemotherapy according to histology. However, randomized trials who led to the approval of antifolate in mesothelioma did not include analysis of outcomes by histology. The objective of this study is to characterize the impact of chemotherapy according to histology in p with MPM at our institution. Methods: We review 189 MPM p diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient’s characteristics: median age 68 years (y) (45-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 75%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed). Median overall survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio

Malignant pleural mesothelioma (MPM) frequently express elevated AKT/mTOR activity. Previous reports in gliomas, colon, breast and prostate cancer suggest that PTEN/PI3K pathway may be important for the induction of PD-L1 expression. This study explored the expression of PTEN/PI3K pathway and PD-L1 in MPM and its relationship with the patient́s prognosisTwenty seven consecutive MPM patients were reviewed. Formalin-fixed, paraffin-embedded tissue biopsies were used for immunohistochemical analysis of PTEN/PI3K pathway and PD-L1 RESULTS: Expression of PTEN, mTOR, pAKT, p4EBP1, peif4E, pS6 and FOXO3a was found in 88.5%, 92.3%, 78.3%, 38.5%, 100%, 52.2% and 100% of tumors and PD-L1 in 23%. We found a significant correlation between pAKT, FOXO3a and PD-L1 expression and longer overall survival (p 0.05). We did not identify significant association between the level of PD-L1 expression and alterations in PI3K pathwayThis study shows PTEN/PI3K pathway and PD-L1 in MPM are frequently activated. Our results suggests that there is not association between PD-L1 and the involvement of the PI3K pathway in MPM.

Non-small-cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases, with a world-wide annual incidence of around 1.3 million. Surgery remains the corner stone of treatment in early-stage NSCLC when feasible, and the addition of adjuvant cisplatin-based chemotherapy has improved these results in resected NSCLC patients. For those patients with non-metastatic NSCLC not suitable for complete surgical resection, chemotherapy plus radiotherapy remains the best treatment option. For patients with metastatic NSCLC, molecular targeted agents have become part of the therapeutic arsenal in recent years. However, to date no targeted agent has been approved for patients with early or locally-advanced stages of NSCLC. Here, we review the rationale, literature and studies addressing the role of targeted agents used in the adjuvant setting or as part of chemoradiotherapy regimens.

e20062 Background: The increasing incidence and poor outcome associated with MPM demand identification of effective treatment options. Promising results have been reported with immunotherapy (IO) in a small proportion of MPM patients (p). MMR deficiency (dMMR) has been well described in several malignancies and was recently approved as a tumor biomarker for IO with anti-PD-1 checkpoint inhibitor. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM p. Methods: Tumors of 159 MPM p from Vall d´Hebron University Hospital and October 12th University Hospital diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR when any MMR protein expression was negative and MMR intact when all MMR proteins were positively expressed. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: P characteristics: median age: 69 years (29-88 years), males: 71%, performance status (PS) 1:69%, asbestos exposure: 52%, stage III at diagnosis: 42%, epithelial subtype: 65%, systemic treatment 81% (57% chemotherapy with cisplatin plus pemetrexed in first line), 50% received second line and 28% third line. MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8m). In a multivariate model factors associated to improved mOS were PS 0 vs PS2 (13 v 2 m, HR 12.8, p < 0.01), neutrophil-lymphocyte ratio (NLR) < 5 (18 v 9 m in NLR ≥5,HR 1.5, p < 0.05) and epitheliod vs sarcomatoid histology (18 vs 4 m HR 4.7, p < 0.01). Thirteen p received IO with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1m). Conclusions: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate novel predictive biomarkers benefit from IO in MPM.

Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis.There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p0.0001).A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

Background Pertuzumab, a dimerization inhibitor of human epidermal growth factor receptor 2 (HER2), has demonstrated pharmacodynamic activity, with stable disease in non–small-cell lung cancer. Combining erlotinib and pertuzumab may enhance antitumor activity. This study aimed to establish the recommended dosing of the erlotinib and pertuzumab combination; assess safety, preliminary efficacy, and pharmacokinetics; and analyze biomarkers. Patients and Methods Fifteen patients with stage IIIb/IV non–small-cell lung cancer who failed chemotherapy were recruited. The patients received erlotinib (days −8 to −1), then combination therapy (21-day cycles for 6 cycles). Pertuzumab was given intravenous at 840 mg, then 420 mg once every three weeks, with erlotinib given daily (100 or 150 mg). Results No dose-limiting toxicities were observed. Adverse events were generally grade 1/2 and manageable. The objective response rate was 20% (3/15 patients; 2 responders had mutant HER1, 1 responder had wild-type HER1), median overall progression-free survival was 9.3 weeks. High HER1, HER2, and HER3 messenger RNA expression correlated with increased progression-free survival. Combination therapy did not affect erlotinib's pharmacokinetics; however, pertuzumab mean exposures (maximum concentration, 231 mg/L; area under the concentration-time curve from 0 to 21 days, 1780 mg*d/L) were slightly higher than in previous studies. Conclusions Combination therapy was well tolerated in patients with good performance status, with encouraging efficacy. A loading dose of pertuzumab 840 mg followed by 420 mg once every three weeks plus daily erlotinib 150 mg appears to be the most appropriate regimen for this combination.

Neutrophil to lymphocyte ratio (NLR), an index of systemic inflammation, has been associated with worse survival for many types of cancer. The aim of this study is to investigate the clinical significance of the blood NLR as a prognostic factor in non-small cell lung cancer (NSCLC) patients. Stage IV NSCLC patients diagnosed in our institution between April 2004 and March 2009 were retrospectively reviewed. Potential prognostic factors such as histology, gender, performance status, response to chemotherapy and NLR were analyzed. NLR was assessed baseline and during chemotherapy treatment. Overall survival (OS) and progression free survival (PFS) were calculated by the Kaplan–Meier method. A total of 171 patients were included in the study and 60 patients (35.1 %) presented a NLR ≥5. Median survival for the entire cohort was 9.3 months. We found that patients with undifferentiated carcinoma and patients with NLR ≥5 had a worse survival. Median PFS of patients with NLR

Background Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm with elevated AKT/mTOR activity. We aimed to identify the expression and phosphorylation status of PTEN, PI3K and downstream signaling in MPM. Patients and methods Thirty consecutive MPM patients were identified. Clinical data analyzed: sex, age, histology, performance status (PS), white blood count, and neutrophil–lymphocyte ratio (NLR). Paraffin-embedded biopsies were used for immunohistochemical analysis. Results Overexpression of PTEN, pMAPK, mTOR, pAKT, 4E-BP1, p4E-BP1, eIF-4E, peIF-4E, p-S6 and FOXO3a in MPM was found in 90%, 100%, 93.3%, 80%, 100%, 43.3%, 96.7%, 100%, 63.3% and 100% of tumors respectively. There was a significant correlation between low pS6 protein expression and longer progression free survival (PFS: 7.9 vs 5.6 months; p =0.04) and overall survival (OS: 23.4 vs 5.6 months; p =0.05). Patients with concomitant low expression of pS6 and p4E-BP1 and overexpression of FOXO3a had significantly better prognosis (34.6 vs 1.9 months; p =0.004). In multivariate analysis, histology and NLR were independent prognostic factors ( p =0.02 and p =0.04 respectively), but pS6 only showed a trend ( p =0.8). Conclusions This study shows PI3K pathway and downstream proteins in MPM are frequently activated and provides prognostic information. The role of PI3K pathway is worth of prospective validation in future studies on MPM.

Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC.Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases.Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P.05). PFS in patients with elevated CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P.05). The OS in patients with high and normal levels of tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P.001).In our analysis, high levels of tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients.

Non-small-cell lung cancer (NSCLC) accounts for 80% of all lung cancer, which is the leading cause of cancer mortality. The majority of NSCLC patients present with advanced disease at diagnosis. Standard chemotherapy using platinum-containing doublets has reached a therapeutic plateau with a median survival of ~1 year. The development of more effective strategies in the first-line setting remains challenging. In selected chemotherapy-naïve, advanced, non-squamous patients, the combination of bevacizumab with chemotherapy was shown to produce better outcomes than chemotherapy alone. The potential benefit of maintenance/sequential treatment after initial platinum-based chemotherapy should be discussed in detail with each patient. Epidermal growth factor receptor (EGFR) mutation determination should be carried out in subgroups of patients characterized by a high prevalence of sensitizing mutations. When a mutation is present, first-line treatment with an EGFR tyrosine kinase inhibitor may be considered. Finally, a phase I study using an oral ALK inhibitor has produced promising results in NSCLC patients with ALK rearrangements, indicating that ALK represents a new therapeutic target in a molecularly defined subset of NSCLC. Ongoing studies in first-line therapy are focusing on targeted therapies and patient selection.

Summary Background Inhibition of the EGFR pathway is a useful strategy in the treatment of patients with advanced NSCLC. The aim of this study is to assess predictive clinical parameters of efficacy. Methods and patients Sixty-two patients with advanced NSCLC were treated with erlotinib as second–third line (150 mg/day). Baseline patient characteristics were: performance status (PS) 1: 92%; median age, 58 years; males, 73%; adenocarcinoma, 45%; current/former smokers, 83%. During erlotinib treatment, 35% of patients had no rash, 32.3% had grade 1 rash, 26% had grade 2 rash and 6.5% patients developed grade 3 rash. Results For patients with grades 2–3 rash vs. those with grades 0–1 rash, time to tumor progression (TTP) and overall survival (OS) were 92 vs. 41 days (p = 0.0381) and 244 vs. 131 days (p = 0.011), respectively. For patients with non-smoking history and current/former smokers, TTP and OS were 136 vs. 42 days (p = 0.0015) and 324 vs. 133 days (p = 0.0242), respectively. In addition, rash grade and smoking history were found to have a highly significant impact on TTP and OS, according to the Cox model. Conclusions Grade ≥2 rash and non-smoking history are associated with improved TTP and OS in advanced NSCLC patients treated with erlotinib.

Purpose: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non–small cell lung cancer patients refractory to platinum-based chemotherapy. Experimental Design: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment. Results: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease ≥12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit. Conclusion: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.

Background. Salivary ductal carcinoma (SDC) is an uncommon malignant tumor of the salivary glands. Although there is no known standard of care for the treatment of ad- vanced disease, the vast majority of patients with SDC may be offered palliative systemic therapy. We report a case of epi- dermal growth factor receptor 2 (HER2)-positive metastatic submandibular SDC with a complete and durable clinical response to treatment with trastuzumab in combination with chemotherapy. Methods and Results. A 62-year-old man was diagnosed with SDC of the left submandibular gland with extensive cervical lymph node involvement. The lesion was completely resected, and the patient underwent postoperative radiotherapy. After 6 months, multiple pulmonary metastatic lesions were detected. A complete response was reached with trastuzumab-based com- bination therapy, and no evidence of disease progression has been observed after 14 months of initiation of systemic therapy. Conclusion. Trastuzumab-based combination therapies should be considered for advanced SDC. V C 2007 Wiley Periodicals, Inc. Head Neck 30: 680-683, 2008

e20526 Background: The most frequent genetic alteration in advanced NSCLC is KRASm in ~25% of tumors. This event associates with smoking pattern and high mutational burden, which correlate with the efficacy of CI in NSCLC. There is in silico evidence that coexisting KRASm and TP53m positively impact immuneCI benefit , but this association needs clinical validation. Methods: We retrospectively assess the efficacy of PD-1/PDL-1 CI (atezolizumab, pembrolizumab, nivolumab or durvalumab) in a cohort of NSCLC patients whose tumors were KRASm (with or without coexisting TP53m) as assessed by a next-generation sequencing test. Endpoints were clinical benefit rate (CBR), defined as partial response or stable disease > 4 months (m), and time to progression (TTP) on immuneCI. Fisher-exact test and log-rank test P values are described. Results: 25 pacients were identified, 68% female, median age 54 y (33-75), 95% former/current smoker; 95% adenocarcinoma; 59% with 2 or more metastatic sites; 36% immuneCI as third-line or beyond (median time from first-line to immuneCI of 7.5 m). 20 tumors had KRASm in codon 12, 3 codon 13 and 2 in codon 61. Overall, CBR was 36% (CI95% 19%-57%) and median TTP was 3.7 m (CI95% 2.2-NA). Coexisting KRASm/ TP53m (n = 11) did not associate with higher CB (27% vs 50%, p = 0.56). A trend for lower TTP in the KRASm/ TP53m vs TP53 wild-type was observed (2.1 vs 5.6 m, HR 0.3; p = 0.11). Conclusions: NSCLC patients whose tumors are KRASm can have substantial benefit with immuneCI. In our series, the population with KRASm/ TP53m tumors did not derive higher clinical benefit from this therapeutic intervention

e20555 Background: EGFR mutant(EGFRm) NSCLC patients develop adquired resistance after 12 months on EGFR TKI. Acquired T790mutation(T790M) is the most common mechanism of resistance in around 60% of patients, followed by MET amplification in 20% of cases. Inclusion in a clinical trials at progression may have an impact in patients’ outcome. Methods: We retrospectively assessed the overall survival in EGFRm patients according to post-progression treatment on 1st/2nd generation EGFR TKI: standard vs. experimental (clinical trial). Also, we assessed the survival in the cohort of acquired T790M NSCLC patients(p). X2 test and long rank test P values are described. OS was defined since progression 1st/2nd generation EGFR TKI to death or last follow up Results: 42p EGFRm were enrolled. According to EGFRm subtype (24 p EGFR del19, 14p EGFR L858R, 1p EGFR exon18, 1 EGFR exon20 ,2p unknown). Median age was 58 (33-83) and 27 (64%) females. First-line EGFR TKI was 30% gefitinib / 58 % erlotinib /10 % afatinib/2% dacotinib At PD, in 51 biopsies (b) were performed,11p were biopsy twice.Tumor tissue for molecular determinations was available in in 86% of cases. Druggable molecular alterations were detected in 57% of cases: 20 acquired T790M and 4 MET amplification. According to these results all 24 p were enrolled in a clinical trial (NCT02108964,NCT01802632,NCT02147990,NCT02335944, NCT02151981), and 18p were screening failure; 8p (45%) of them due to abscense of adquired resistance mechanisms. 10 received platinum-based chemotherapy and 6 only received best supportive care. OS metastatic disease was 51 months for patients included in a clinical trial vs 22 months for those on standard treatment (p < 0.001; 95%CI: 14.4-47). OS was: 34 months vs 10 months for those included in a clinical trial vs standard, respectively (p < 0.001; 95%CI: 8.88-25). For T790M tumours, OS post-progression was 25 months Conclusions: Enrolling patients in clinical trials may allow personalised treatment according to mechanisms of resistance improving survival after 1st/2nd generation EGFR TK progression disease.

BackgroundAnaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients.MethodsNSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR) at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3) was explored.Resultsninety-nine patients were identified. Median age was 61.5 years (range 35-83), all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1%) patients were ALK positive by FISH, thirteen (13.1%) were EGFR mutant, and 65 (65.6%) were negative/Wild Type (WT) for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4%) and adenocarcinoma (71.4%). ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative.ConclusionsALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients.

8502Background: MM is an asbestos-induced cancer with increasing global incidence. 1st-line treatment is pemetrexed + platinum; there are no approved 2nd-line therapies. CTLA-4 is a co-inhibitory r...

Purpose of review Approximately 50% of surgically resected early stage lung cancer patients will relapse and die of recurrent disease within 5 years. In order to reduce the risk of relapse and improve survival, efforts have been focused on the use of chemotherapy before or after surgery. The benefit of adjuvant cisplatin-based chemotherapy is widely accepted for patients with resected stage II-IIIA, although its impact on survival is limited. There is, therefore, a need to find other strategies to further improve survival outcomes. Recent findings In recent years, there has been a marked increase in the development of novel therapeutic strategies targeting signaling pathways, such as epidermal growth factor receptor, angiogenesis, and immunotherapy in stage IV nonsmall cell lung cancer. The potential contribution of these strategies in the adjuvant setting is now being analyzed in randomized clinical trials. Summary At present, the challenge for research in early stage disease is to define subsets of patients who benefit from certain targeting agents and establish how to integrate such agents into the adjuvant setting.

Purpose To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated. Methods Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50 mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25 mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m 2 days 1, 8) and cisplatin (80 mg/m 2 day 1). Results A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses. Conclusions The MTD was identified as sunitinib 37.5 mg (Schedule 2/1), gemcitabine 1250 mg/m 2 , and cisplatin 80 mg/m 2 , with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.

Lung cancer is the leading cause of cancer death world wide. Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung carcinomas [1]. Approximately one-third of NSCLC patients are diagnosed with early disease and for these patients surgery is the most effective treatment with an intent-to-cure. Despite complete surgical excision, 50% of patients with stage IB, 70% of stage II and a higher percentage of patients with stage III NSCLC relapse and the majority die of their disease. Following surgery, distant recurrence is the most common form of relapse and eventual cause of death. Since distant disease is the most common failure pattern following surgery in early stages of NSCLC, adjuvant chemotherapy is a rational therapeutic strategy for such patients.

Background: Aberrant MET activation occurs in many types of malignancies and includes protein overexpression, increased gene copy number, amplifications, mutations and deletions. The frequency of genomic alterations in MET varies widely among solid tumors. The criteria for MET amplification and MET overexpression have not been established as well as the relationship between MET amplification, MET expression and additional genomic alterations known to be important in tumor biology. Previous and current phase 1 clinical trials have selected patients without matching MET criterion. Materials and Methods: From Dec/2012 to Dec/2014, 203 formalin fixed paraffin embedded tumor samples from 197 patients consented to undergo targeted MET analysis. Samples were 117 primary and 86 metastatic tumors. Tumor types included colorectal, gastric, lung, glioblastoma, and breast. Samples were analyzed by fluorescence in situ hybridization (FISH) for MET gene amplification (MET/CEN-7 FISH Zytolight SPEC assay Z-2087, Zytovision), and by immunohistochemistry (IHC) for MET protein expression [Met (D1C2) XP® Rabbit mAb #8198, Cell signaling]. Mutations in key oncogenes were determined using Sequenom (Mass Array) and Amplicon-Mi Seq (Illumina) Cancer Panel. Results: MET gene copy number variation (>5copies) was found in 11 of 203 samples (5%) and MET gene amplification (based on the definition of MET/CEN-7 ≥2.2) was found in 6 of 203 samples (3%). Eleven (5%) samples had ≥4 or ≤5 copies of MET gene. KRAS mutation was found in 28 of 167 samples (17%) and PIK3CA mutation in 6 of 167 samples (4%). Both mutations were observed in tumor samples with < 4 copies of MET gene. MET IHC positive (≥ 50% positive cells 3+) was found in 11 of 203 samples (5%). Seven of 203 samples (3%) had MET IHC positive (≥ 50% positive cells 3+ and 2+). MET protein expression showed statistical association with MET gene copy number (P Conclusion: MET expression is higher in metastatic than primary tumor samples. There is a significant association between MET expression and gene copy number. High MET copy number was more frequent in tumors without KRAS and PIK3CA mutation. Quantitative MET protein expression data will be presented. MET IHCMET FISH≥ 50% cells 3+≥ 50% cells 3+ and 2+< 50% cells 3+and 2+< 2 copies01 (0.7%)40 (28.2%)2- 5 copies5 (3.5%)04 (2.8%) Citation Format: Analía Azaro, Guillem Argilés, María Alsina, Elena Elez, Teresa Macarulla, Cristina Cruz, Donatella Marino, Cinta Hierro, Susana Cedres, Alejandro Navarro, María Ochoa de Olza, Irene Braña, Juan Martín-Liberal, Marta Vilaró, Debora Moreno, Paola Martínez, María Díaz, Ana Vivancos, Jordi Rodón, Josep Tabernero, Ludmila Prudkin, Paolo Nuciforo. Prevalence of MET copy number variation, MET expression and MET related genomic alterations in all solid tumors pre-screening program. VHIO experience. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B187.